The present invention relates to an automated procedure for optical analysis of structures, in particular, for analysis and determination of biological, cellular structures, as well as an apparatus for this purpose.
To help with disease recognition, microscopic changes of components and structures can be used along with chemical and biological analysis of samples from biological organisms to determine presence of diseases and monitor their progression. To simplify these types of biological and chemical determinations, increased automation is being used. This reduces cost and increases speed. Microscopic observations, however, are still performed by an experienced person.
Apparatuses for automated and semi-automated analyses of chemical and biological substances and parameters are generally known. For example, WO 2006/00015 describes an apparatus and a process for arranging pipettes and dispenser tips in a system for manipulating liquid samples. Such an apparatus includes a robotic manipulator for aligning pipettes and dispenser tips in direction X and at a right angle to this in direction Y in or on sample holders arranged within the system. Such apparatus typically also include the ability to move pipettes and dispenser tips vertically up and down, in the direction Z, with respect to the directions X and Y. It is advantageous if the sample holders can be directed along the workbench. Liquid samples can be present in the wells of microtiter plates or can be pipetted into these from sample tubes. Typically, two microtiter plates are arranged on a so-called plate carrier, which preferably can also be directed along the workbench. This sort of analysis device is distributed by Aesku.Systems GmbH & Co. KG, Wendelsheim, DE under the name Helmed.
CH 696 030 A5 describes an apparatus for manipulation of samples in holders and/or on a slide within a described field X-Y, in which the first and second robotic manipulators are able to be used on at least the entire area of the X-Y field, without interfering with one another. The field of action for both robotic manipulators can be freely selected. The second robotic manipulator is able to pass by the first robotic manipulator both, when loaded or unloaded with objects. The relocation of diverse objects by the second robotic manipulator, such as transfer of active devices such as scanners (1 D, 2D), cameras, printheads, etc., enables use of these devices across the entire field of the working platform.
A storage unit for biological samples consisting essentially of a main horizontal surface with multiple storage chambers is described in EP 1 829 613 A1. Biological samples, such as tissue samples obtained by biopsy, are often stored as tissue pieces in cassettes or thin sections on slides for use in biological laboratories, and in particular in pathology laboratories within universities and hospitals. A selection of such cassettes and glass slides is provided, for example, by Thermo Shandon.
In WO 2005/103725 A1, an apparatus for transporting or studying fluids in a system for working with liquid samples is described. The apparatus includes at least one functional element with at least one functional end, whereby the functional element is generally perpendicular (vertical) to the working field in a Z-direction.
DE 10 2007 018 483 A1 describes a working platform for handling of liquids, such as pipetting of liquids from receptacles and their distribution in wells of a microtiter plate, generally known through the documents WO 02/059626 A1 (entitled “Pipetting Device”) and EP1 477 815 A1 (entitled “Device for precisely approaching microplate wells”). In particular, the invention describes working platforms in which for example, pipette tips are brought automatically to a particular location.
In WO 2007/071613 A1, an apparatus for conditioning system fluids for a liquid handling device is described, wherein the following state of the art is referred to. Branches of industry, such as pharmaceutical research and in clinical diagnostics, which involve biochemical techniques, require installations for processing of liquid volumes and fluid samples. Automated installations typically include a liquid handling device, such as a single pipetting device or multiple pipetting devices that can be used with fluid reservoirs located on the workbench of a workstation, or form part of a liquid handling workstation.
EP 1 206 967 A2, describes that a droplet with a volume of greater than 10 μl can simply be released into the air because, with correct use of the pipette the droplet exits the pipette tip of its own accord. The droplet size is dependent on the physical characteristics of the sample fluid, such as surface tension and viscosity. Thus the drop size limits dispersion of the quantity of liquid to be dispensed. EP 0 725 267 A2 describes a pipette tip in the form of a microinjection pump with which a fluid sample can be actively separated. Subsequently delivery of fluid occurs via the hydrostatic pressure in the tubing between storage reservoir and pipette tip.
Under the presently known systems such as those known for example in WO 2006/000115 A1. WO 02/059626 A1 and EP 1 477 815 A1, it is common that all eight wells or positions of a microtiter plate are simultaneously filled and washed, and reagents added using eight equidistant hollow needles (cannula).
EP 1 921 552 describes a network controlled procedure for ensuring authenticity and quality of visually obtained laboratory diagnostic findings based on manual or semi-automated medical laboratory analyses using indirect immunofluorescence. By electronically networking the sample processing steps the laboratory system used for this minimizes human sources of error, while at the same time guaranteeing that visually obtained findings depend on a correct and error free patient sample associated data base. Nevertheless, the visually obtained findings depend on an assessment of the fluorescence patterns obtained and are therefore based on a manual step.
It is often necessary to optically study biological and chemical reactions of biological systems using for example tissue fragments, whole cells or even cell components such as cell organelles. This is achieved by viewing and analyzing the objects of study under a microscope, whereby to date this typically involves visual assessment and sorting based on the subjective experience of the user.